Deficiency of the complex I of the mitochondrial respiratory chain but improved adenylate control over succinate-dependent respiration are human gastric cancer-specific phenomena.

Abstract

The purpose of study was to comparatively characterize the oxidative phosphorylation (OXPHOS) and function of respiratory chain in mitochondria in human gastric corpus mucosa undergoing transition from normal to cancer states and in human gastric cancer cell lines, MKN28 and MKN45. The tissue samples taken by endobiopsy and the cells were permeabilized by saponin treatment to assess mitochondrial function in situ by high-resolution oxygraphy. Compared to the control group of endobiopsy samples, the maximal capacity of OXPHOS in the cancer group was almost twice lower. The respiratory chain complex I-dependent respiration, normalized to complex II-dependent respiration, was reduced that suggests deficiency of complex I, but the respiratory control by ADP in the presence of succinate was increased. Similar changes were observed also in mucosa adjacent to cancer tissue. The respiratory capacity of MKN45 cells was higher than that of MKN28 cells, but both types of cells exhibited a deficiency of complex I of the respiratory chain which appears to be an intrinsic property of the cancer cells. In conclusion, human gastric cancer is associated with decreased respiratory capacity, deficiency of the respiratory complex I of mitochondria, and improved coupling of succinate oxidation to phosphorylation in tumor tissue and adjacent atrophic mucosa. Detection of these changes in endobiopsy samples may be of diagnostic value.

• Authors: Marju Puurand, Nadežda Peet, Andres Piirsoo, Margot Peetsalu, Jaan Soplepmann, Meeli Sirotkina, Ants Peetsalu, Akseli Hemminki, Enn Seppet
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 370 Issue 1-2 Pg. 69-78 (Nov 2012) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 22821176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine Diphosphate
• Succinic Acid
• Electron Transport Complex I

Topics

• Adenosine Diphosphate (metabolism)
• Aged
• Cell Line, Tumor
• Cell Respiration (drug effects)
• Electron Transport (drug effects)
• Electron Transport Complex I (deficiency, metabolism)
• Female
• Gastric Mucosa (drug effects, metabolism, pathology)
• Humans
• Male
• Mitochondria (drug effects, metabolism)
• Oxidative Phosphorylation (drug effects)
• Stomach Neoplasms (metabolism, pathology, ultrastructure)
• Succinic Acid (pharmacology)